Gaps in communication between different staff groups and older adult patients foster unnecessary antibiotic prescribing for urinary tract infections in hospitals: a qualitative translation approach.

Background: Studies have reported large scale overprescribing of antibiotics for urinary tract infection (UTI) in hospitalised older adults. Older adults often have asymptomatic bacteriuria, and clinicians have been found to diagnose UTIs inappropriately based on vague symptoms and positive urinalysis and microbiology. However, the joined perspectives of different staff groups and older adult patients on UTI diagnosis have not been investigated. Methods: Thematic analysis of qualitative interviews with healthcare staff (n = 27) and older adult patients (n = 14) in two UK hospitals. Results: Interviews featured a recurrent theme of discrepant understandings and gaps in communication or translation between different social groups in three key forms: First, between clinicians and older adult patients about symptom recognition. Second, between nurses and doctors about the use and reliability of point-of-care urinary dipsticks. Third, between nurses, patients, microbiologists and doctors about collection of urine specimens, contamination of the specimens and interpretation of mixed growth laboratory results. The three gaps in communication could all foster inappropriate diagnosis and antibiotic prescribing. Conclusion: Interventions to improve diagnosis and prescribing for UTIs in older adults typically focus on educating clinicians. Drawing on the sociological concept of translation and interviews with staff and patients our findings suggest that inappropriate diagnosis and antibiotic prescribing in hospitals can be fuelled by gaps in communication or translation between different staff groups and older adult patients, using different languages and technologies or interpreting them differently. We suggest that interventions in this area may be improved by also addressing discrepant understandings and communication about symptoms, urinary dipsticks and the process of urinalysis.

Reduction in methicillin-resistant Staphylococcus aureus colonisation: impact of a screening and decolonisation programme.

Patients in care homes are often at 'high risk' of being methicillin-resistant Staphylococcus aureus (MRSA) colonised. Here we report the prevalence of MRSA, the effect of MRSA screening and decolonisation in Wolverhampton care-home residents. Eighty-two care homes (1665 residents) were screened for MRSA, three times at 6-monthly intervals (referred to as phases one, two and three). Screening and decolonisation of MRSA-colonised residents led to a reduction in the prevalence of MRSA from 8.7% in phase one, 6.3% in phase 2 and 4.7% in phase three. Overall, the study suggests that care-home facilities in Wolverhampton are a significant reservoir for MRSA; screening and decolonisation has reduced the risk to residents going for procedures and has indirectly impacted on MRSA rates in the acute Trust.

Is there any value in measuring faecal calprotectin in Clostridium difficile positive faecal samples?

Markers of intestinal inflammation have been proposed for inclusion in Clostridium difficile diagnostic algorithms. Faecal calprotectin (f-Cp), a sensitive marker of intestinal inflammation, was evaluated for utility in C. difficile diagnosis in the hospital setting. One hundred and twenty C. difficile positive and 99 C. difficile negative faecal samples of hospital-acquired diarrhoea were analysed for f-Cp using a quantitative ELISA. C. difficile positivity was confirmed using ELISAs for either toxins (n = 45) or glutamate dehydrogenase (GDH) with toxin gene confirmation (n = 75). Non-parametric ANOVA (Kruskal-Wallis) was used for data analysis. C. difficile positive samples had higher (P<0.05) median (interquartile range) f-Cp levels; 336 µg g(-1) (208-536) for toxin and 249 µg g(-1) (155-498) for GDH and toxin gene positive compared with 106 µg g(-1) (46-176) for C. difficile and culture-negative faecal samples. Five C. difficile positive samples were f-Cp negative (<50 µg g(-1)). A f-Cp concentration >50 µg g(-1) was 96 % sensitive and 26 % specific for C. difficile, with area under the ROC curve of 0.82. There is no role for f-CP alone in predicting C. difficile infection in hospital-acquired diarrhoea due to its low specificity.

Good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults in the UK: a consensus statement.

These good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) are an update to a previous consensus statement on OPAT in the UK published in 1998. They are based on previous national and international guidelines, but have been further developed through an extensive consultation process, and are underpinned by evidence from published literature on OPAT. They provide pragmatic guidance on the development and delivery of OPAT services, looking at all aspects of service design, care delivery, outcome monitoring and quality assurance, with the aim of ensuring that OPAT services provide high-quality, low-risk care, whatever the healthcare setting. They will provide a useful resource for teams developing new services, as well as a practical set of quality indicators for existing services.

Evolution of cold-tolerant fungal symbionts permits winter fungiculture by leafcutter ants at the northern frontier of a tropical ant-fungus symbiosis.

The obligate mutualism between leafcutter ants and their Attamyces fungi originated 8 to 12 million years ago in the tropics, but extends today also into temperate regions in South and North America. The northernmost leafcutter ant Atta texana sustains fungiculture during winter temperatures that would harm the cold-sensitive Attamyces cultivars of tropical leafcutter ants. Cold-tolerance of Attamyces cultivars increases with winter harshness along a south-to-north temperature gradient across the range of A. texana, indicating selection for cold-tolerant Attamyces variants along the temperature cline. Ecological niche modeling corroborates winter temperature as a key range-limiting factor impeding northward expansion of A. texana. The northernmost A. texana populations are able to sustain fungiculture throughout winter because of their cold-adapted fungi and because of seasonal, vertical garden relocation (maintaining gardens deep in the ground in winter to protect them from extreme cold, then moving gardens to warmer, shallow depths in spring). Although the origin of leafcutter fungiculture was an evolutionary breakthrough that revolutionized the food niche of tropical fungus-growing ants, the original adaptations of this host-microbe symbiosis to tropical temperatures and the dependence on cold-sensitive fungal symbionts eventually constrained expansion into temperate habitats. Evolution of cold-tolerant fungi within the symbiosis relaxed constraints on winter fungiculture at the northern frontier of the leafcutter ant distribution, thereby expanding the ecological niche of an obligate host-microbe symbiosis.

Development of a novel ozone- and photo-stable HyPer5 red fluorescent dye for array CGH and microarray gene expression analysis with consistent performance irrespective of environmental conditions.

BACKGROUND: Array-based comparative genomic hybridization (CGH) and gene expression profiling have become vital techniques for identifying molecular defects underlying genetic diseases. Regardless of the microarray platform, cyanine dyes (Cy3 and Cy5) are one of the most widely used fluorescent dye pairs for microarray analysis owing to their brightness and ease of incorporation, enabling high level of assay sensitivity. However, combining both dyes on arrays can become problematic during summer months when ozone levels rise to near 25 parts per billion (ppb). Under such conditions, Cy5 is known to rapidly degrade leading to loss of signal from either "homebrew" or commercial arrays. Cy5 can also suffer disproportionately from dye photobleaching resulting in distortion of (Cy5/Cy3) ratios used in copy number analysis. Our laboratory has been active in fluorescent dye research to find a suitable alternative to Cy5 that is stable to ozone and resistant to photo-bleaching. Here, we report on the development of such a dye, called HyPer5, and describe its' exceptional ozone and photostable properties on microarrays. RESULTS: Our results show HyPer5 signal to be stable to high ozone levels. Repeated exposure of mouse arrays hybridized with HyPer5-labeled cDNA to 300 ppb ozone at 5, 10 and 15 minute intervals resulted in no signal loss from the dye. In comparison, Cy5 arrays showed a dramatic 80% decrease in total signal during the same interval. Photobleaching experiments show HyPer5 to be resistant to light induced damage with 3- fold improvement in dye stability over Cy5. In high resolution array CGH experiments, HyPer5 is demonstrated to detect chromosomal aberrations at loci 2p21-16.3 and 15q26.3-26.2 from three patient sample using bacterial artificial chromosome (BAC) arrays. The photostability of HyPer5 is further documented by repeat array scanning without loss of detection. Additionally, HyPer5 arrays are shown to preserve sensitivity and data quality from gene expression experiments. CONCLUSION: HyPer5 is a red fluorescent dye that behaves functionally similar to Cy5 except in stability to ozone and light. HyPer5 is demonstrated to be resistant to ozone at up to 300 ppb, levels significantly higher than commonly observed during summer months. Consequently, HyPer5 dye can be used in parallel with Cy3 under any environmental conditions in array experiments.

Human immature monocyte-derived dendritic cells express the G protein-coupled receptor GPR105 (KIAA0001, P2Y14) and increase intracellular calcium in response to its agonist, uridine diphosphoglucose.

Dendritic cells (DC) are essential to the initiation of an immune response due to their unique ability to take-up and process Ag, translocate to lymph nodes, and present processed Ag to naive T cells. Many chemokines, chemokine receptors and other G protein-coupled receptors (GPCRs) are implicated in these various aspects of DC biology. Through microarray analysis, we compared expression levels of chemokines, their cognate receptors, and selected GPCRs in human monocytes and in vitro monocyte-derived immature and mature DC. Hierarchical clustering of gene expression clearly distinguishes the three cell types, most notably highlighting exceptional levels of expression of the GPCR GPR105 within the immature monocyte-derived DC (MDDC) gene cluster. Little or no expression was observed within the monocyte and mature MDDC cluster. Putative functionality of the GPR105 receptor was demonstrated by an observed calcium flux in immature MDDC treated with the potent GPR105 agonist, uridine 5'-diphosphoglucose (UDP-glucose), while no response to the nucleotide sugar was seen in monocytes and mature MDDC. This UDP-glucose-induced calcium response was, at least in part, pertussis toxin-sensitive. Moreover, immature MDDC from some donors treated with UDP-glucose exhibit an increase in expression of the costimulatory molecule CD86, which correlates with the intensity of the UDP-glucose-induced calcium flux. Together, these data demonstrate differential expression of GPR105 on immature and mature MDDC and suggest a role for the receptor and its agonist ligand in DC activation.